1,4-Dioxane → Methyl 3-fluoro-11-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[b]quinoline-1-carboxylate

HRID 521413노트

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HRID 521413 반응식
O=[C:2]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[C:9]([O:11]C)=O.[NH2:13][C:14]1[CH:15]=[C:16]([CH:21]=[C:22]([F:24])[CH:23]=1)[C:17]([O:19][CH3:20])=[O:18].O1CCOCC1>O>[F:24][C:22]1[CH:21]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[C:15]2[C:9](=[O:11])[C:3]3[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:2]=3[NH:13][C:14]=2[CH:23]=1

참가 물질

5

반응물 3

HCID 312751,4-DioxaneHCID 288225Methyl 2-oxocycloheptane-1-carboxylateHCID 3807862Methyl 3-amino-5-fluorobenzoate

생성물 1

HCID 89669535Methyl 3-fluoro-11-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[b]quinoline-1-carboxylate수율 107.2%

시약·촉매·용매 1

HCID 962Water용매

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온도
130 °C

실험 절차

A mixture of methyl 2-oxocycloheptanecarboxylate (0.34 g, 2 mmol), methyl 3-amino-5-fluorobenzoate (0.33 g, 2 mmol), polyphosphoric acid (4.0 g) and dioxane (5 mL) was heated at 130° C. for 5 hours. After cooling to room temperature, the solution was diluted with water (100 mL), and NaOAc.3H2O (7.3 g) was added. Then the resulting precipitate was collected by filtration and dried. The solid was suspended in methanol (20 mL) and SOCl2 (10 mL) was added, the mixture was stirred at reflux for 5 hours, concentrated and treated with water (50 mL), extracted with ethyl acetate (3×50 mL). The organic layer was separated, concentrated and the residue was chromatographed to give the crude product (0.62 g). MS (ESI) m/e [M+1]+290.0.

후처리

  1. temperatureAfter cooling to room temperature
  2. additionwas added
  3. filtrationThen the resulting precipitate was collected by filtration
  4. customdried
  5. additionSOCl2 (10 mL) was added
  6. temperatureat reflux for 5 hours
  7. concentrationconcentrated
  8. additiontreated with water (50 mL)
  9. extractionextracted with ethyl acetate (3×50 mL)
  10. customThe organic layer was separated
  11. concentrationconcentrated
  12. customthe residue was chromatographed

출처 및 근거

ORD 기록
ord-a937d8b4fc3f45eb803ae03ae362bce1
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09328111B2

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